重型肝炎时乙型肝炎病毒基因型与基本核心启动子及前C区突变关系的研究

目的探讨重型肝炎（重肝）乙型肝炎病毒（HBV）基因型与基本核心启动子（BCP）及前C区突变的关系。方法采用聚合酶链反应（PCR）-限制性片段长度多态性分析技术（PCR-RFLP）对52例重肝和52例慢性乙肝（CHB）进行HBV基因分型。采用PCR产物直接测序技术，随机对15例B型和15例C型重肝患者的BCP区和前C区进行序列测定，分析HBV基因型与BCPT1762／A1764及前C区A1896突变的关系。结果泉州地区重肝的基因型以B型为主（48．08％），其次为C型（30．77％）和B／C混合型（17．31％），无A、E、F型存在。与CHB组比较，重肝组B型检出率明显降低，而C型和BIC混合型检出率明显升高。C型重肝患者BCPT1762／A1764双突变率显著高于B型（P〈0．05），而前C区A1896突变率在B、C型感染者中差异无统计学意义（P〉0．05）。结论C型感染易引起较重肝损伤，而B／C型混合感染可能是导致重肝发生的重要原因之一。C型重肝患者BCP T1762／A1764双突变率显著高于B型。

Relationship between hepatitis B virus genotypes and basic core promoter/precore mutations in patients with severe hepatitis

Objective To investigate the relationship between hepatitis B virus genotypes and basic core promoter (BCP)/precore mutations in patients with severe hepatitis.Methods HBV genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 52 patients with severe hepatitis and 52 cases with chronic hepatitis B (CHB). Eight samples of genotypes B and C were randomly selected and their S gene was directly sequenced, and then their phylogenetic trees were analyzed. Fifteen samples of each of genotypes B and C were randomly selected and their BCP and precore genes were directly sequenced with PCR, and then the relationship between genotypes and BCP(T1762/A1764)/precore (A1896)mutations were analyzed. Results Genotype B,C and mixed genotypes (B and C) were detected in patients with severe hepatitis in Quanzhou area. Genotype B was the majority with a proportion 48.08%,others had a proportion 30.77% and 17.31%,respectively. Genotype A, E and F were not detected. The percents of genotype C, mixed B and C in severe hepatitis were significantly higher than that in CHB. The double mutation in BCP (T1762/A1764) was significantly more frequent in severe hepatitis with genotype C than that in genotype B (P<0.05). However, there was no significant difference in the distribution of precore mutant with A1896 between genotype B and C patients (P>0.05).Conclusions Genotype C may induce more severe liver inflammation than that genotype B may do. Mixed genotypes B and C infection may be an important determinant of inducing severe hepatitis. The double mutation in BCP (T1762/A1764) was more common in severe hepatitis with genotype C than that with genotype B.